1. ACUTE KIDNEY INJURY

2. Anatomy of the Kidney Cardiac Output Approximately 1,200 ml of blood or 25 % of flows through the kidney in one minute Renal artery and vein Fibrous capsule Cortex Pelvis Pyramid (medulla) Ureter Deep inside the cortex and the medulla regions are long hairpin-like structures called nephrons, these are the functional urine producing unit of the kidney © 2012 – Michel Helmy 2

3. The Nephron The urine producing part of the kidney Distal tubule Collecting duct Loop of Henle Peritubular capillaries Proximal tubule Bowman’s capsule Glomerulus Afferent arteriole (wider) Efferent arteriole (narrow ) There are one million Nephrons in each kidney The efferent arteriole, which is narrower than the afferent arteriole, creating a hydrostatic pressure in glomerulus © 2012 – Michel Helmy 3

4. Renal Function Secretion of three different hormones: SECRETORY FUNCTIONEXCRETORY FUNCTION Renin: regulate blood pressure Vitamin D: regulate calcium uptake Excretion product of the kidney: urine EPO: regulate red blood cell production Remove excess fluid Remove waste products Urea & Creatinine Regulate acid/base balance Regulate electrolyte levels © 2012 – Michel Helmy 4

5. Definition: AKI = ARF? AKI = Acute Kidney Injury Intended to describe the entire spectrum of disease from being relatively mild to severe. © 2012 – Michel Helmy 5 ARF = Acute Renal Failure Defined as renal function inadequate to clear the waste products of metabolism despite the absence of correction of hemodynamic or mechanical causes. Clinical manifestations of renal failure include the following: Uremic symptoms (drowsiness, nausea, hiccough, twitching) Hyperkalemia Hyponatremia Metabolic acidosis Defined as an abrupt change in serum creatinine and/or urine output and classified according the RIFLE criteria

6. Definition of AKI Acute kidney injury (AKI) is defined as any of the following (Not Graded): Increase in SCr by ≥ 0.3 mg/dl ( ≥ 26.5 µmol/l) within 48 hours; OR Increase in SCr to ≥ 1.5 times baseline, which is known or presumed to have occurred within prior 7 days OR Urine volume <0.5 ml/kg/h for 6 hours © 2012 – Michel Helmy 6

7. Conclusion: AKI is not ARF As you have seen, the terms acute kidney injury (AKI) and acute renal failure (ARF) are not synonymous. While the term renal failure is best reserved for patients who have lost renal function to the point that life can no longer be sustained without intervention, AKI is used to describe the milder as well as severe forms of acute renal dysfunction in patients. Let us have a deeper look at the classification of AKI… © 2012 – Michel Helmy 7

8. Traditional classification of ARF Post-renal ARF Intrinsic-renal ARF The causes of ARF are traditionally divided into three categories. Although this division is useful for classification, all three categories may occur simultaneously in a given patient. ARF is a complication that can occur following any medical condition. It can result from pre-renal causes, intrinsic renal causes or post-renal causes. Acute Renal Failure Pre-renal ARF © 2012 – Michel Helmy 8

9. Pre-renal ARF Kidney hypoperfusion (reduced blood supply) results in both renal ischemia (reduced supply of oxygenated blood) and low GFR By far the most commonly type of ARF seen in ICUseen Common causes: intravascular volume depletion dehydration, hemorrhage decreased cardiac output congestive heart failure, infarct systemic vasodilatation (dilation of blood vessels) anaphylactic shock, sepsis Acute Renal Failure © 2012 – Michel Helmy 9

10. Intrinsic ARF Possible causes: miscellaneous renal diseases toxins Necrosis (is Greek for dead) = death of cell and living tissue Tubule is part of the Nephron, the urine forming part of the kidneykidney Acute Renal Failure Intrinsic renal causes account for 35-40% of ARF cases. The causes of intrinsic renal failure are diseases or toxins causing damage of the small renal vessels and glomeruli, commonly resulting in acute tubular necrosis. © 2012 – Michel Helmy 10

11. Post-renal ARF Increased pressure on the Bowman’s capsule offers a resistance to normal filtration pressure, which causes an acute reduction in GFRFR Cause: acute obstruction of the flow of urine Acute Renal Failure Post-renal causes account only for about 5% of ARF cases. They are associated with acute obstruction of the flow of urine which can occur at any point in the urinary tract. The obstruction creates a back flow of urine in the kidney which results in an increased pressure on The Bowman’s capsule. The constant pressure offers a resistance to the normal filtration pressure, which causes an acute reduction in GRF. © 2012 – Michel Helmy 11

12. Causes of AKI Volume-responsive AKI © 2012 – Michel Helmy 12 Postoperative AKIHypotension Sepsis-induced AKI Now let’s go back to the concept of AKI! AKI is common in the critically ill, especially in patients with sepsis and other forms of systemic inflammation (e.g. major surgery, trauma, burns), but other causes must be considered. Let us look at the 4 most common causes first:

13. ADQI (Acute Dialysis Quality Initiative) is a process initiated by a group of physicians from different parts of the world, with the objective to seek consensus and evidence and establish guidelines towards AKI. They have proposed the RIFLE classification as a definition of AKI. RIFLE defines three grades of severity of ARF on the basis of either an acute increase in serum creatinine, decrease in GFR or decreased urine output. Risk Injury Failure Outcome: Loss End-stage renal disease AKI … Stages (RIFLE Criteria) 20

14. Classification of AKI according to RIFLE criteria RIFLE defines three grades of severity of AKI on the basis of either: acute increase in serum creatinine decrease in GFR decreased urine output. Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004 Gambro Acute Therapies supports the RIFLE definition of AKI © 2012 – Michel Helmy 21

15. 22 Staging of AKI 2.1.2: AKI is staged for severity according to the following criteria (below). (Not Graded) StageSerum CreatinineUrine Output 11.5-1.9 times baseline OR ≥0.3 mg/dl (≥ 26.5 µmol/l) increase <0.5 ml/kg/h for 6-12 hours 22.0-2.9 times baseline <0.5 ml/kg/h for ≥12 hours 3 3.0 times baseline OR increase in serum creatinine to ≥4.0 mg/dl (≥ 353.6 µmol/l) OR initiation of renal replacement therapy OR, in patients <18 years, decrease in eGFR to <35 ml/min per 1.73 m 2 <0.3 ml/kg/h for ≥ 24 hours OR Anuria for ≥ 12 hours

16. RIFLE criteria: Urine Output Approximately 50-60% of AKI cases are non-oliguric Patients may continue to make urine despite an inadequate glomerular filtration Although prognosis is often better if urine output is maintained, use of diuretics to promote urine output does not seem to improve outcome (and some studies even suggests harm) Anuria: <100 ml/24 hour Oliguria: 100-400 ml/24 hour Nonoliguria: >400 ml/24 hour Definition Now when do we talk of ‘Oliguria’? And when is a patient ‘non-oliguric’? © 2012 – Michel Helmy 16

17. Diagnostic work up 1. Urinalysis: Microscopic evaluation of urinary sediment. Presence of few formed elements or hyaline casts is suggestive of prerenal or postrenal azotemia. Many RBCs may suggest calculi, trauma, infection or tumor Eosinophilia : occurs in 95 % of patients with acute allergic nephritis Brownish pigmented cellular casts and many renal epithelia cells are seen in patients with acute tubular necrosis (ATN )

18. Pigmented casts without erythrocytes in the sediment from urine but with positive dipstick for occult blood indicates hemoglobinuria or myoglobinuria

19. Dipstick test : trace or no proteinuria with pre-renal and post-renal AKI; mild to moderate proteinuria with ATN and moderate to severe proteinuria with glomerular diseases. RBCs and RBC casts in glomerular diseases Crystals, RBCs and WBCs in post-renal ARF.

20. 2. Urine and blood Chemistry: Most of these tests help to differentiate prerenal azotemia, in which tubular reabsorption function is preserved from acute tubular necrosis where tubular reabsorption is severely disturbed. Osmolality or specific gravity: decreased in ATN and pos-renal AKI (urine is diluted) while increased in pre-renal AKI ( urine is concentrated)

21. BUN/plasma creatinine ratio: the BUN/plasma creatinine ratio is normal at 10-15:1 in ATN, but may be greater than 20:1 in prerenal disease due to the increase in the passive reabsorption of urea that follows the enhanced proximal transport of sodium and water. Thus, a high ratio is highly suggestive of prerenal disease as long as some other cause is not present. But this criterion is not highly specific.

22. FE Na Fractional excretion of Na+: is ratio of urine-to- plasma Na ratio to urine-to-plasma creatinine expressed as a percentage [ (UNa/PNa)/(Ucr/Pcr )X 100]. Value below 1% suggest prerenal failure, and values above 1% suggest ATN Serum K+ and other electrolytes

23. 3. Radiography/imaging Ultrasonography: helps to see the presence of two kidneys, for evaluating kidney size and shape, and for detecting hydronephrosis or hydroureter. It also helps to see renal calculi, and renal vein thrombosis. Retrograde pyelography: is done when obstructive uropathy is suspected

24. Management of AKI 1. Prevention: Because there are no specific therapies for ischemic or nephrotoxic AKI, intravascular volume in high-risk patients Many cases of ischemic AKI can be avoided by close attention to cardiovascular function and intravascular volume in high-risk patients, such as the elderly and those with preexisting renal insufficiency.

25. Aggressive restoration of intravascular volume has been shown to reduce the incidence of ischemic AKI dramatically after major surgery or trauma, burns, or cholera prevention is of paramount importance.

26. The incidence of nephrotoxic ARF can be reduced by tailoring the dosage of potential nephrotoxins to body size and GFR; for example, reducing the dose or frequency of administration of drugs in patients with preexisting renal impairment

27. Maintenance of urine output: Loop diuretics may be usefully to convert the oliguric form of ATN to the nonoliguric form. High doses of loop diuretics such as Furosemide (up to 200 to 400 mg intravenously) may promote diuresis in patients who fail to respond to conventional doses

28. Look for cause and treat Specific Therapies: To date, there are no specific therapies for established intrinsic renal ARF due to ischemia or nephrotoxicity. Management of these disorders should focus on elimination of the causative hemodynamic abnormality or toxin, avoidance of additional insults, and prevention and treatment of complications. Specific treatment of other causes of intrinsic renal ARF depends on the underlying pathology.

29. Prerenal ARF: The composition of replacement fluids for treatment of prerenal ARF due to hypovolemia must be tailored according to the composition of the lost fluid. Severe hypovolemia due to hemorrhage should be corrected with packed red blood cells, whereas isotonic saline is usually appropriate replacement for mild to moderate hemorrhage or plasma loss (e.g., burns, pancreatitis).

30. Urinary and gastrointestinal fluids can vary greatly in composition but are usually hypotonic. Hypotonic solutions (e.g., 0.45% saline) are usually recommended as initial replacement in patients with prerenal ARF due to increased urinary or gastrointestinal fluid losses, although isotonic saline may be more appropriate in severe cases

31. Subsequent therapy should be based on measurements of the volume and ionic content of excreted or drained fluids. Serum potassium and acid-base status should be monitored carefully.

32. Postrenal ARF: Management of postrenal ARF requires close collaboration between nephrologist, urologist, and radiologist. Obstruction of the urethra or bladder neck is usually managed initially by transurethral or suprapubic placement of a bladder catheter, which provides temporary relief while the obstructing lesion, is identified and treated definitively. Similarly, ureteric obstruction may be treated initially by percutaneous catheterization of the dilated renal pelvis or ureter.

33. 4. Supportive Measures: (Conservative therapy ) Dietary management: Generally, sufficient calorie reflects a diet that provides 40-60 gm of protein and 35-50 kcal/kg lean body weight. In some patients, severe catabolism occurs and protein supplementation to achieve 1.25 gm of protein /kg body weight is required to maintain nitrogen balance. Restricting dietary protein to approximately 0.6 g/kg per day of protein of high biologic value (i.e., rich in essential amino acids) may be recommended in sever azotemia.

34. Fluid and electrolyte management : Following correction of hypovolemia, Total oral and intravenous fluid administration should be equal to daily sensible losses (via urine, stool, and NG tune o surgical drainage ) plus estimated insensible ( i.e., respiratory and derma ) losses which usually equals 400 – 500 ml/day. Strict input output monitoring is important.

35. Hypervolemia: can usually be managed by restriction of salt and water intake and diuretics. Metabolic acidosis: is not treated unless serum bicarbonate concentration falls below 15 mmol/L or arterial pH falls below 7.2. More severe acidosis is corrected by oral or intravenous sodium bicarbonate.

36. Initial rates of replacement are guided by estimates of bicarbonate deficit and adjusted thereafter according to serum levels. Patients are monitored for complications of bicarbonate administration such as hypervolemia, metabolic alkalosis, hypocalcemia, and hypokalemia. From a practical point of view, most patients requiring sodium bicarbonate need emergency dialysis within days.

37. Hyperkalemia: cardiac and neurologic complications may occur if serum K+ level is > 6.5 mEq/L o Restrict dietary K+ intake o Give calcium gluconate 10 ml of 10% solution over 5 minutes o Glucose solution 50 ml of 50 % glucose plus Insulin 10 units IV o Give potassium –binding ion exchange resin o Dialysis: it medial therapy fails or the patient is very toxic

38. Hyperphosphatemia is usually controlled by restriction of dietary phosphate and by oral aluminum hydroxide or calcium carbonate, which reduce gastrointestinal absorption of phosphate. Hypocalcemia does not usually require treatment.

39. Anemia: may necessitate blood transfusion if severe or if recovery is delayed. GI bleeding: Regular doses of antacids appear to reduce the incidence of gastrointestinal hemorrhage significantly and may be more effective in this regard than H2 antagonists, or proton pump inhibitors. Meticulous care of intravenous cannulae, bladder catheters, and other invasive devices is mandatory to avoid infections

40. Dialysis Indications and Modalities of Dialysis: - Dialysis replaces renal function until regeneration and repair restore renal function. Hemodialysis and peritoneal dialysis appear equally effective for management of ARF. Absolute indications for dialysis include: Symptoms or signs of the uremic syndrome Refractory hypervolemia Sever hyperkalemia Metabolic acidosis.

41. Patients with no complicating factors who survive an episode of acute renal failure have a 90 % chance of complete recovery of kidney function.

42. RECOVERY Complete Renal Recovery is defined when: Serum Creatinine (S Crt ) is not more than 50% increased from baseline example: if baseline S Crt is 1 mg/dL (88 mmol/L) complete recovery is said to occur if the new steady state S Crt is <1.5 mg/dL (133 mmol/L) Partial Renal Recovery is defined when: The above condition for complete recovery is not met but the patient does not require chronic dialysis (i.e. renal ‘loss’ has not occurred)